Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary...

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Veröffentlicht in:	Journal of the American Society of Nephrology Jg. 25; H. 10; S. 2177
Hauptverfasser:	Sabbisetti, Venkata S, Waikar, Sushrut S, Antoine, Daniel J, Smiles, Adam, Wang, Chang, Ravisankar, Abinaya, Ito, Kazumi, Sharma, Sahil, Ramadesikan, Swetha, Lee, Michelle, Briskin, Rebeccah, De Jager, Philip L, Ngo, Thanh Thu, Radlinski, Mark, Dear, James W, Park, Kevin B, Betensky, Rebecca, Krolewski, Andrzej S, Bonventre, Joseph V
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.10.2014
Schlagworte:	Adult Aged Aged, 80 and over Animals Biomarkers - blood Case-Control Studies Cell Adhesion Molecules - blood Diabetes Mellitus, Type 1 - complications Diabetic Nephropathies - blood Female Hepatitis A Virus Cellular Receptor 1 Humans Male Membrane Glycoproteins - blood Membrane Proteins - blood Mice, Inbred BALB C Middle Aged Rats, Sprague-Dawley Receptors, Virus - blood Renal Insufficiency - blood Young Adult chronic kidney disease acute renal failure nephrotoxicity chronic kidney failure
ISSN:	1533-3450, 1533-3450
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Abstract	Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.
AbstractList	Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury. Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.
Author	Ravisankar, Abinaya Radlinski, Mark Lee, Michelle Wang, Chang Briskin, Rebeccah Ngo, Thanh Thu Sharma, Sahil Antoine, Daniel J Betensky, Rebecca Bonventre, Joseph V Ramadesikan, Swetha Ito, Kazumi Park, Kevin B Krolewski, Andrzej S Waikar, Sushrut S Sabbisetti, Venkata S Dear, James W Smiles, Adam De Jager, Philip L
Author_xml	– sequence: 1 givenname: Venkata S surname: Sabbisetti fullname: Sabbisetti, Venkata S organization: Renal Division, Department of Medicine and – sequence: 2 givenname: Sushrut S surname: Waikar fullname: Waikar, Sushrut S organization: Renal Division, Department of Medicine and – sequence: 3 givenname: Daniel J surname: Antoine fullname: Antoine, Daniel J organization: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom – sequence: 4 givenname: Adam surname: Smiles fullname: Smiles, Adam organization: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts – sequence: 5 givenname: Chang surname: Wang fullname: Wang, Chang organization: Renal Division, Department of Medicine and – sequence: 6 givenname: Abinaya surname: Ravisankar fullname: Ravisankar, Abinaya organization: Renal Division, Department of Medicine and – sequence: 7 givenname: Kazumi surname: Ito fullname: Ito, Kazumi organization: Renal Division, Department of Medicine and – sequence: 8 givenname: Sahil surname: Sharma fullname: Sharma, Sahil organization: Renal Division, Department of Medicine and – sequence: 9 givenname: Swetha surname: Ramadesikan fullname: Ramadesikan, Swetha organization: Renal Division, Department of Medicine and – sequence: 10 givenname: Michelle surname: Lee fullname: Lee, Michelle organization: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts – sequence: 11 givenname: Rebeccah surname: Briskin fullname: Briskin, Rebeccah organization: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts – sequence: 12 givenname: Philip L surname: De Jager fullname: De Jager, Philip L organization: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts – sequence: 13 givenname: Thanh Thu surname: Ngo fullname: Ngo, Thanh Thu organization: Renal Division, Department of Medicine and – sequence: 14 givenname: Mark surname: Radlinski fullname: Radlinski, Mark organization: Renal Division, Department of Medicine and – sequence: 15 givenname: James W surname: Dear fullname: Dear, James W organization: British Heart Foundation for Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; and – sequence: 16 givenname: Kevin B surname: Park fullname: Park, Kevin B organization: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom – sequence: 17 givenname: Rebecca surname: Betensky fullname: Betensky, Rebecca organization: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts – sequence: 18 givenname: Andrzej S surname: Krolewski fullname: Krolewski, Andrzej S organization: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts – sequence: 19 givenname: Joseph V surname: Bonventre fullname: Bonventre, Joseph V email: vsabbisetti@partners.org, joseph_bonventre@hms.harvard.edu organization: Renal Division, Department of Medicine and vsabbisetti@partners.org joseph_bonventre@hms.harvard.edu
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24904085$$D View this record in MEDLINE/PubMed
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Copyright	Copyright © 2014 by the American Society of Nephrology.
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Keywords	chronic kidney disease acute renal failure nephrotoxicity chronic kidney failure
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Snippet	Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is...
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SubjectTerms	Adult Aged Aged, 80 and over Animals Biomarkers - blood Case-Control Studies Cell Adhesion Molecules - blood Diabetes Mellitus, Type 1 - complications Diabetic Nephropathies - blood Female Hepatitis A Virus Cellular Receptor 1 Humans Male Membrane Glycoproteins - blood Membrane Proteins - blood Mice, Inbred BALB C Middle Aged Rats, Sprague-Dawley Receptors, Virus - blood Renal Insufficiency - blood Young Adult
Title	Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes
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